Accidental Falls/statistics & numerical data; Aged; Aged, 80 and over; Alendronate/administration & dosage/adverse effects; Algorithms; Bone Density/drug effects; Bone Density Conservation Agents/administration & dosage/adverse effects; Cholecalciferol/administration & dosage/adverse effects; Diphosphonates/adverse effects/therapeutic use; Drug Combinations; Female; Humans; Osteoporosis, Postmenopausal/complications/drug therapy; Postmenopause/drug effects/physiology; Standard of Care; Vitamin D Deficiency/complications/drug therapy
Abstract :
[en] Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D(3) 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients' personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score </=2.5 or </=1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8-20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took >/=800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (-57% vs. -46%, P < 0.001) and bone-specific alkaline phosphatase (-47% vs. -40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D-insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.
Disciplines :
General & internal medicine
Author, co-author :
Ralston, Stuart H
Binkley, Neil
Boonen, Steven
Kiel, Douglas P
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Roux, Christian
Chen, Liang
Rosenberg, Elizabeth
Santora, Arthur
Language :
English
Title :
Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency.
Publication date :
2011
Journal title :
Calcified Tissue International
ISSN :
0171-967X
eISSN :
1432-0827
Publisher :
Springer Verlag, New York, United States - New York
Gaugris S, Heaney RP, Boonen S, Kurth H, Bentkover JD, Sen SS (2005) Vitamin D inadequacy among post-menopausal women: a systematic review. QJM 98:667-676 (Pubitemid 41236096)
Norman AW, Bouillon R, Whiting SJ, Vieth R, Lips P (2007) 13th Workshop consensus for vitamin D nutritional guidelines. J Steroid Biochem Mol Biol 103:204-205 (Pubitemid 46420528)
Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266-281
Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J (2006) The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med 260:245-254 (Pubitemid 44253638)
Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE (2005) Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90:3215-3224 (Pubitemid 41014278)
Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P (2009) Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. J Bone Miner Res 24:693-701
Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, Hollis BW, Drezner MK (2007) Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab 92:2130-2135 (Pubitemid 46997111)
Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T (2001) A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the Multiple Outcomes of Raloxifene Evaluation clinical trial. J Clin Endocrinol Metab 86:1212-1221 (Pubitemid 32323007)
Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B (2004) Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 116:634-639 (Pubitemid 38490539)
Geller JL, Hu B, Reed S, Mirocha J, Adams JS (2008) Increase in bone mass after correction of vitamin D insufficiency in bisphosphonate-treated patients. Endocr Pract 14:293-297
Kamel S, Brazier M, Rogez JC, Vincent O, Maamer M, Desmet G, Sebert JL (1996) Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency. J Clin Endocrinol Metab 81:3717-3721 (Pubitemid 26339944)
Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477-501
van Schoor NM, Visser M, Pluijm SM, Kuchuk N, Smit JH, Lips P (2008) Vitamin D deficiency as a risk factor for osteoporotic fractures. Bone 42:260-266
Ooms ME, Roos JC, Bezemer PD, van der Vijgh WJ, Bouter LM, Lips P (1995) Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 80:1052-1058
Prestwood KM, Pannullo AM, Kenny AM, Pilbeam CC, Raisz LG (1996) The effect of a short course of calcium and vitamin D on bone turnover in older women. Osteoporos Int 6:314-319 (Pubitemid 26280826)
von Hurst PR, Stonehouse W, Kruger MC, Coad J (2010) Vitamin D supplementation suppresses age-induced bone turnover in older women who are vitamin D deficient. J Steroid Biochem Mol Biol 121:293-296
Bischoff-Ferrari H, Dawson-Hughes B, Staehelin H, Orav J, Stuck A, Theiler R, Wong J, Egli A, Kiel D, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:b3692
Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P (2007) Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 92:1415-1423 (Pubitemid 46556419)
Segal E, Zinman C, Raz B, Ish-Shalom S (2009) Low patient compliance - a major negative factor in achieving vitamin D adequacy in elderly hip fracture patients supplemented with 800 IU of vitamin D3 daily. Arch Gerontol Geriatr 49:364-367
Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O'Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669-683 (Pubitemid 43247138)
Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621-1628 (Pubitemid 40693411)
Adami S, Giannini S, Bianchi G, Sinigaglia L, Di Munno O, Fiore CE, Minisola S, Rossini M (2009) Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos Int 20:239-244
Writing Committee on Behalf of the HDFP Cooperative Group (1976) The Hypertension Detection and Follow-Up Program. Prev Med 5:207-215
Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB (1995) Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332:556-561
Guralnik JM, Ferrucci L, Pieper CF, Leveille SG, Markides KS, Ostir GV, Studenski S, Berkman LF, Wallace RB (2000) Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci 55:M221-M231 (Pubitemid 30257618)
Liang K-Y, Zeger SL (2000) Longitudinal data analysis of continuous and discrete response for pre-post designs. Indian J Stat 62:134-148
Bonnick S, Saag KG, Kiel DP, McClung M, Hochberg M, Burnett SM, Sebba A, Kagan R, Chen E, Thompson DE, de Papp AE (2006) Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years. J Clin Endocrinol Metab 91:2631-2637 (Pubitemid 44024629)
